I’m skeptical about … cannabis (part 2)

Most people harbor guilty pleasures. Mine have nothing to do with marijuana, but I do admit to a weakness for good spy thrillers, and it’s my interest in the latter that led me to write this post about the former. Alex Berenson, an ex-New York Times reporter, is the author of my favorite spy series about a CIA operative named John Wells. You can learn a lot about covert operations from reading this series, so when Berenson turned his attention to a non-fiction book warning about the dangers of cannabis called, Tell Your Children: The Truth About Marijuana, Mental Illness, and Violence, it got my attention. The basic premise is that marijuana not only worsens schizophrenia and other mental illnesses, but can actually cause psychosis and violence in people not otherwise predisposed to it. The book is not without flaws; it too often smears the line between association and causation, while relying too heavily on anecdotes of heinous crimes to establish the connection between marijuana and violence (I also found the lack of an index and annotated bibliography troublesome). Still, the read provoked enough interest to send me scurrying for the primary sources, including the exhaustive National Academy of Sciences cannabis report issued in 2017. While the Academy’s review found evidence of benefit for just 3 indications (chronic pain, chemotherapy induced nausea, and MS-related muscle spasticity), the same report cited evidence of harm across a number of health-related concerns.

 

 

Overall, 9% of marijuana users will become addicted to it. That number increases to 17% in teens and runs between 25 to 50% of daily users, wherein addiction is defined as having two or more of the following:

  • Tolerance (i.e. requiring greater amounts to achieve the same effect).
  • Withdrawal (i.e. physical and psychological symptoms related to the drug’s removal).
  • Increasing frequency and quantity of drug use over time.
  • Unsuccessful attempts to stop using.
  • Preoccupation with use at the expense of other activities.
  • Ongoing use despite physical and/or psychological symptoms related to use.
  • Increasing time spent in obtaining and using the drug.
  • Hazardous use.
  • Social/interpersonal problems related to use.
  • Craving.
  • Neglecting major roles (social, occupational, and/or family) due to use.

The percentage of marijuana users who become addicted should give you pause because it’s the same percentage as people receiving opioid prescriptions who become addicted to them, tranquilizer users who become addicted to benzodiazepines, or drinkers who become alcoholics. It’s simply a myth that marijuana isn’t addictive, or is less addictive than other drugs. And although it’s virtually impossible to kill yourself by overdosing on it, this represents a very poor yardstick by which to measure safety.

 

(NEJM 2014; 370: 2219.)

 

Over the years there has been a lot of controversy about whether marijuana is a “gateway drug,” meaning a drug that leads to the use of other, more dangerous drugs. Always seemed like nonsense to me: Isn’t it the personality of the individual that predisposes them to drug use, not the drug that predisposes the individual? For a substance to act as a gateway drug, it would have to alter brain chemistry in such a way as to render the individual more susceptible to the lure of other drugs (i.e. change the personality of the user). Although difficult to prove via a randomized controlled trial, there is a growing body of observational evidence that marijuana—particularly when used early in life—does just that. Remember, too, that observational evidence, when overwhelming, is adequate to establish cause and effect. There are still no randomized controlled trials demonstrating that cigarettes cause cancer, but does anybody doubt the relationship? No researcher is going to randomize teens into smoking, or not smoking marijuana, and then see how many of them go on to use harder drugs. Observational data is all we have, and all we’re ever likely to have on this topic.

Let’s start with the simple observation that marijuana frequently precedes more serious drug use, like cocaine, amphetamines, and heroin. The National Academy of Sciences report found “moderate evidence of a statistical association between cannabis use and the development of substance dependence and/or a substance abuse disorder.” But this isn’t enough to establish cause and effect. Maybe people predisposed to addiction simply try marijuana along with a bunch of other drugs before finally becoming addicted to something. To further investigate the connection, 219 sets of same sex Dutch twins were followed from adolescence into early adulthood. In the sets where one twin started using cannabis before age 18 and the other didn’t, the subsequent use of hard drugs like cocaine and heroin, or party drugs like ecstasy, was substantially higher. The lifetime use of hard drugs was more than 7-fold higher in early cannabis users compared to their co-twin (12.8% versus 1.7%), party drug use more than 4-fold higher (16.2% versus 3.8%), and ongoing regular cannabis use more than 3-fold higher (16.2% versus 5.1%). Although this doesn’t prove that early marijuana use leads to harder drugs, it suggests that it has the potential to rewire reward pathways in a manner predisposing to it. Given the twins’ shared genetics (nature) and upbringing (nurture), this is as close as we’re going to get to a controlled trial.

 

(www.recoveryfirst.org)

 

Subsequently, Australian researchers examined more than 4,000 pairs of twins born between 1972-79 and followed them regarding drug use and the subsequent development of mental illness and substance use disorders. The data noted a strong inverse relationship between the age of onset of cannabis use among twins and the subsequent development of abuse and addiction to marijuana and other illicit drugs. For example, while 36.8% of those who used cannabis before age 16 reported cocaine use later in life, only 13.2% of those using cannabis for the first time after age 20 reported the same, compared with just 1.1% of people who had never used cannabis. While this might be interpreted to mean that people who like drugs simply use them earlier in life, the association between early cannabis use and later hard drug use is unique to cannabis and persists after controlling for the use of alcohol or other drugs.

A recent meta-analysis on the harmful effects of marijuana found a number of trials demonstrating structural changes within the brains of marijuana users compared to non-users, as measured by MRI and PET scans. Furthermore, the areas of structural change (amygdala, hippocampus, white-grey matter) correspond to regions of the brain responsible for the behavioral and functional changes seen in marijuana users (altered memory, learning, and attention). It’s also true that the brain’s dopamine pathways responsible for the release of “reward” neurotransmitters contain CB1 and CB2 receptors. To summarize: There is solid data linking marijuana to behavioral changes corresponding to structural brain changes, coupled with the observation of accelerated drug use in twins who use marijuana during early adolescence. Taken together, it’s entirely plausible that marijuana alters the brain’s reward pathways in a manner predisposing it to other drugs (i.e. marijuana = gateway drug). These findings surprised me, but that’s the beauty of science; it cares not for our surprise.

 

MRI Demonstrating Areas of Diminished Gray Matter in Cannabis Users (NIH: Nat’l Institute on Drug Abuse, www.drugabuse.gov).

 

In the short term, marijuana negatively impacts memory, learning, and attention based on a number of studies employing validated neuropsychiatric testing. This is not controversial. Marijuana users are far more likely to drop out of high school than non-users. The greater the use, the greater the drop-out rate. High school stoners are rarely valedictorians. The good news is that short-term learning deficits disappear when the drug is stopped.

 

(Nat’l Academy of Sciences, “The Health Effects of Cannabis and Cannabinoids,” Nat’l Academies Press, 2017).

 

As for long term use, high cumulative exposure worsens cognitive functioning. In a study of 3,385 participants followed for 25 years, those with ongoing use and high lifetime use scored significantly worse on memory testing (as determined by the ability to memorize and retrieve 15-word lists). Additionally, ongoing use into middle-age worsened performance across other domains like processing speed (visual motor speed, sustained attention, and working memory) and executive functioning (the ability to view multiple visual stimuli and respond to one stimulus while suppressing others). Again, no surprise. Despite what Willie Nelson might say, high frequency, long-term marijuana use isn’t healthy for the brain (although it might not detract from the ability to write a good country song).

 

(Biolog Psych 2016; 79: 557.)

 

Marijuana impairs motor skills. Do you want your kids’ bus driver to be high when taking them to school? How about your Uber driver at 3 AM? Or even the barista mixing up your cinnamon cloud macchiato? Given that a third of marijuana users report daily use, there’s a good chance that this is already happening if you live in a state where marijuana is legal for recreational use. The odds of being in a car crash are more than 2-times higher when driving under the influence of cannabis compared to driving unimpaired. This is essentially the same risk associated with driving while intoxicated with an alcohol level of 0.08%. And while the metabolism of THC based on the route of ingestion (smoking versus edibles) makes blood testing problematic, it’s simply irresponsible for legislators to have legalized cannabis without first having establishing criteria for impairment and how to test for it.

 

(Nat’l Academy of Sciences, “The Health Effects of Cannabis and Cannabinoids,” Nat’l Academies Press, 2017).

 

The first recreational sales of marijuana began in Colorado in 2014. Since then, ER visits for accidental pediatric exposures have increased by more than 85%, visits for all-cause marijuana complaints by 73%, and calls to Poison Control for cannabis-related concerns by 74%. The number of ER visits for cannabinoid hyperemesis syndrome (repetitive vomiting related to marijuana) in Colorado have doubled. And this is just the beginning. The fact that marijuana is safer than some other drugs doesn’t mean that it’s safe.

 

(NEJM 2014; 370: 2219)

 

Inhaled marijuana increases the risk of COPD and chronic bronchitis. Comparing marijuana to tobacco, one joint is more irritative than one cigarette, but since people rarely smoke 20 joints a day, the net effect on lung function is less severe in marijuana smokers than tobacco smokers. The risk of lung cancer does not appear to be higher in cannabis users than non-users (although studies suggest an increased risk of testicular cancer in male users).

Marijuana slightly increases the risk of heart attack, stroke, and brain bleeds proximate to use. The risk is small but since the harms are large, why take the chance? Meanwhile, the results of studies on overall mortality associated with cannabis use are mixed. While the National Academy of Sciences report concluded the data insufficient to make a determination, a study of more than 50,000 Swedish men followed over 40 years noted a higher all-cause mortality in marijuana users, while another population-based study of more than 45,000 California patients admitted with a diagnosis of cannabis dependence and followed over 16 years found a 4-fold increased all-cause mortality relative to the general population. Although neither study establishes cause and effect, the takeaway here is that cannabis and the lifestyle surrounding its use are likely hazardous to your health.

 

(Nat’l Academy of Sciences, “The Health Effects of Cannabis and Cannabinoids,” Nat’l Academies Press, 2017).

 

Finally, the elephant in the room—does cannabis cause mental illness, exacerbate pre-existing illness, or neither? Alternatively, might it be a treatment? The first observational study demonstrating a link between marijuana and psychosis appeared in The Lancet way back in 1987. A physician reviewing mental health outcomes in 50,000 male, Swedish military recruits from 1969-1970 noted a striking association between the use of marijuana and the subsequent development of schizophrenia. Even occasional use was associated with a higher risk, but among recruits who admitted to smoking 50 times or more, the subsequent risk of schizophrenia was 6-times higher than in recruits who had never used the drug. Observational trials establish association, not cause and effect, but certainly the study raised the question as to whether marijuana might cause schizophrenia. Proponents for legalization have consistently argued that schizophrenics use marijuana as an anodyne, that it’s a treatment for psychotic symptoms, not a cause of them. This is incorrect.

In 2002, the first prospective trial examining the link was published. More than 1,000 people from Dunedin, New Zealand were followed from birth to age 26. Participants were assessed for mental illness at age 11, and surveyed for drug use at age 15 and 18. The primary endpoint was the development of mental illness by age 26. Cannabis use was found to be an independent risk factor for the development of psychosis, even after controlling for other drug use and the presence of mental illness at age 11. That same year, a follow up study of the Swedish recruits reported on in The Lancet paper also determined cannabis to be an independent risk factor for schizophrenia, the authors concluding: “Cannabis use is associated with an increased risk of developing schizophrenia, consistent with a causal relation. This association is not explained by use of other psychoactive drugs or personality traits relating to social integration.” More data followed. A study of school-age Dutch children and another of Australian siblings found the same thing; early, frequent use of marijuana increased the downstream risk of psychosis. In fact, every study examining the topic has come to the same conclusion.

 

Increasing Odds Ratio of Psychosis versus Increasing Cannabis Use: Results from Various Studies (Schizo Bulletin 2016; 42: 126.)

 

If you already have schizophrenia, marijuana may improve certain aspects of the disease while worsening others. A 2004 study noted an increased incidence of hallucinations and agitation in cannabis patients with schizophrenia. The authors of a Cochrane review on the use of marijuana to treat schizophrenia noted in their Plain Language Summary that: “Clinical evidence suggests people who have schizophrenia have a worse overall outcome from using cannabis.”

As for other types of mental illness, frequent cannabis use increases the risk of developing bipolar disorder, social anxiety disorder, depression, and suicide. While marijuana works for many to reduce near-term anxiety, chronic use likely worsens it. The jury is out on PTSD. Of course, this doesn’t mean that everyone who engages in a bit of weekend weed will end up with mental illness any more than it means that everyone who drinks a cocktail will become an alcoholic, but if you already have a genetic predisposition for these disorders you should think twice. Want to change your state of mind? Try a walk in the woods instead, serenity with no side effects.

 

(Nat’l Academy of Sciences, “The Health Effects of Cannabis and Cannabinoids,” Nat’l Academies Press, 2017).

 

In the end, perhaps the best reason not to legalize cannabis for recreational use comes from what we know about the drugs that are already legal. Tobacco—480,000 annual deaths; alcohol—88,000 annual deaths; prescription opioids—17,000 annual deaths. And this doesn’t count the more than 47,000 suicides where drug use often plays a contributing or causative role. I am not opposed to decriminalization, but it’s hard for me to get behind marijuana outlets at the local mall. I simply don’t see the advantage to legalizing more drugs with the potential for abuse and harm. I admit to personal bias. After more than 30 years of working in ERs, I’ve seen too many lives destroyed because of drugs. The data on cannabis doesn’t provide reassurance. Maybe it will prove to be safer than alcohol. So what? Libertarian values sound good in theory, but fail when put into practice, because society ultimately pays the price for poor individual decision-making. Higher medical costs are just the most obvious, but who can measure the cost of a cannabis-related car accident that kills your daughter, or a lifetime of schizophrenia in a son who smoked weed just to be cool?

 

Bottom Line: Cannabis use increases the risk of car accidents and results in negative short-term effects on attention, memory, and learning. Its use increases the risk of schizophrenia and other mental health disorders, particularly when initiated in early adolescence. Long-term use slightly increases the risk of testicular cancer, COPD, heart attack, stroke, and cognitive decline. The rate of cannabis addiction is similar to that of other drugs of abuse (9%).

 

(For those interested in learning more, but who aren’t up for the 487-page National Academy of Sciences review, I highly recommend the shorter, more digestible World Health Organization report: “The Health and Social Effects of Nonmedical Cannabis Use,” available for free download at https://www.who.int/substance_abuse/publications/msbcannabis.pdf.)

 

Next: CBD oil and synthetics.

Disclosure: Despite my skepticism regarding marijuana legalization, I acknowledge owning stock in several cannabis ventures including Canopy Growth, Aurora Cannabis, CannTrust Holdings, Alternative Harvest ETF, Khiron Life Sciences, and Innovative Industrial Properties.

 

References:

  1. Alex Berenson, Tell Your Children: The Truth About Marijuana, Mental Illness, and Violence (New York: Free Press, 2019).
  2. National Academies of Sciences, Engineering, and Medicine, The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research (2017) (Washington DC: The National Academies Press, 2017).
  3. Nora Volkow, et al., “Adverse Health Effects of Marijuana,” NEJM 2014; 370 (23): 2219-27.
  4. American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders (DSM-5), (Arlington: American Psychiatric Association, 2013).
  5. Michael Lynskey et al., “Early Onset Cannabis Use and Progression to other Drug Use in a Sample of Dutch Twins,” Behavioral Genetics 2006; 36 (2): 195-200.
  6. Ally Memedovich et al., “The Adverse Health Effects and Harms Related to Marijuana Use: An Overview Review,” CMAJ Open 2018; 6 (3): E339-46.
  7. Michael Lynskey et al., “An Australian Twin Study of Cannabis and Other Illicit Drug Use and Misuse, and Other Psychopathology,” Twin Res Human Genetics 2012; 15 (5): 631-41.
  8. Samantha Broyd et al., “Acute and Chronic Effects of Cannabinoids on Human Cognition—A Systematic Review,” Biolog Psych 2015; 79: 557-67.
  9. Reto Auer et al., “Association Between Lifetime Marijuana Use and Cognitive Function in Middle Age: The Coronary Artery Risk Development in Young Adults (CARDIA) Study,” JAMA Int Med 2016; 176 (3): 352-61.
  10. Mark Asbridge et al., “Acute Cannabis Consumption and Motor Vehicle Collision Risk: Systematic Review of Observational Studies and Meta-Analysis,” BMJ 2012; 344: e536.
  11. Howard Kim and Andrew Monte, “Colorado Cannabis Legalization and Its Effect on Emergency Care,” Ann Em Med 2016; 68 (1): 71-75.
  12. Sven Andreasson et al., “Cannabis and Schizophrenia: A Longitudinal Study of Swedish Conscripts,” Lancet 1987; 330 (8574): 1483-86.
  13. Louise Arseneault et al., “Cannabis Use in Adolescence and Risk for Adult Psychosis: Longitudinal Prospective Study,” BMJ 2002; 325 (7374): 1212-13.
  14. Stanley Zammit et al., “Self -Reported Cannabis Use as a Risk Factor for Schizophrenia in Swedish Conscripts of 1969: Historical Cohort Study,” BMJ 2002; 325 (7374): 1199-1203.
  15. Willemijn van Gastel et al., “Cannabis Use and Subclinical Positive Psychotic Experiences in Early Adolescence: Findings from a Dutch Survey,” Addiction 2011; 107: 383-87.
  16. John McGrath et al., “Association Between Cannabis Use and Psychosis-Related Outcomes Using Sibling Pair Analysis in a Cohort of Young Adults,” Arch Gen Psych 2010; 67 (5): 440-47.
  17. Anton Grech et al., “Cannabis Use and Outcome of Recent Onset Psychosis,” Europ Psych 2005; 20: 349-53.
  18. Theresa Moore et al., “Cannabis Use and Risk of Psychotic or Affective Mental Health Outcomes: A Systematic Review,” Lancet 2007; 370: 319-28.
  19. C. McLoughlin et al., “Cannabis and Schizophrenia (Review),” Cochrane Database of Systematic Reviews 2014, Issue 10. Art. No.: CD004837.
  20. Nora Volkow et al., “Effects of Cannabis Use on Human Behavior, Including Cognition, Motivation, and Psychosis: A Review,” JAMA Psych 2016; 73 (3): 292-97.

 

2 thoughts on “I’m skeptical about … cannabis (part 2)

  1. Bob,
    Great post. I think it is clear that people under 25 should avoid cannabis use. Regarding legalization, you fail to address the violence, here and in Mexico, associated with prohibition. Drug cartels and American organized crime (including street gangs) profit enormously from marijuana trafficking. Decriminalization will not solve this issue.
    Chris

    • You may be correct, but that doesn’t make the drug itself any safer, no matter who ultimately peddles it to us. This post is about the individual harms posed by cannabis, and not the socioeconomic effects. I am merely trying to open people’s eyes to the fact that legalization has occurred not because the drug is safe, but because it’s profitable. The choice to use remains individual, and maybe this post will convince a few to avoid it. Light a candle, not a joint.

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